NCAN Summary Engineers and scientists at the National Center for Adaptive Neurotechnologies (NCAN) are creating technologies that can guide CNS plasticity to enhance recovery for people with spinal cord injury, stroke, or other neuromuscular disorders. NCAN is producing new insights and novel therapies and disseminating them to engineers, scientists, and clinicians everywhere. This renewal application proposes to enhance NCAN technologies, apply them to critical problems, hasten their clinical translation, and increase their wider impact. Aim 1 will develop a wholly implanted wireless system for long-term 24/7 interactive studies in freely moving rats. It will use this new system for the first study of the molecular biology underlying spinal reflex operant conditioning, a promising new therapy that can enhance recovery after spinal cord injury or other disorders. This novel system will support many kinds of long-term real-time interactive interventions for NCAN and for other researchers. Aim 2 will develop a robust clinical system that supports a wide variety of protocols designed to target beneficial plasticity to key CNS sites and is suitable for widespread clinical use. It will optimize this new system in collaboration with clinical therapists and provide it for therapeutic studies focused on spinal cord injury, cerebral palsy, and stroke. Aim 3 will develop a clinically practical system that uses electrical stimulation via electrocorticographic/stereoencephalographic electrodes to map brain networks, define causality between areas, and ultimately, to target plasticity that restores function impaired by stroke or other disorders. It will thereby create a new imaging modality that can reveal point-to-point functional connections in the brain, relate them to behavior, and enable their therapeutic modulation. Aim 4 will provide training in and promote dissemination of NCAN neurotechnologies. It will enhance NCAN's 3-week short course curriculum, continue to offer many topic-specific workshops in appropriate venues, and provide materials and guidance that enable other institutions to create their own topic-specific courses. It will disseminate and support training materials and technologies through the NCAN website and other mechanisms. Aim 5 comprises the administration that supports all NCAN activities. This new grant period will include further development of major successes of the first grant period, initiation of new technologies and novel therapeutic protocols, strong synergistic interactions among the Aims, intensive collaborations with industry, and growing focus on clinical translation of NCAN technologies and protocols. In summary, NCAN will continue to create novel neurotechnologies, define their mechanisms, translate them into widespread use, and provide training and dissemination that enable and encourage other scientists, engineers, and clinicians to join in developing these technologies and applying them to major scientific and clinical problems. Thus, NCAN will continue to perform, encourage, and enable studies that elucidate CNS function and dysfunction, and that realize effective new therapies for devastating neurological disorders.